Nucleotide sequence and genomic organization of feline immunodeficiency virus.

Talbott, Randy; Sparger, Ellen E.; Lovelace, K; Fitch, Walter M.; Pedersen, Niels C; Luciw, Paul A.; Elder, John H.

doi:10.1073/pnas.86.15.5743

Cited by 351 publications

(336 citation statements)

References 29 publications

(45 reference statements)

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“…The first FIV vector system was constructed from FIV 34TF10 [38] by a few simple recombinant steps, and established that non-dividing human cells could be efficiently transduced with FIV vectors [8]. This result has now been confirmed by others using similar or modified systems, each of which was also derived from the 34TF10 molecular clone [15,16,19].…”

Section: Optimization Of Fiv Vectorsmentioning

confidence: 56%

“…This restriction is not due to a viral entry block, as the native FIV envelope glycoprotein uses the human chemokine receptor CXCR4 efficiently [35]. In addition, FIV particles do not have potential to provoke immunological cross-reactivity with HIV proteins, for example, in diagnostic HIV antibody ELISAs [36][37][38]; along with other considerations, this could be one factor enhancing acceptance by potential patients and by personnel carrying out large-scale production and use.…”

Section: Introductionmentioning

confidence: 99%

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FIV: from lentivirus to lentivector

Saenz

Poeschla

2004

J. Gene Med.

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SummaryMolecular virological understanding of the feline immunodeficiency virus (FIV) life cycle is increasing, facilitating rational derivation of improved vectors from this non-primate lentivirus. The packaging signal has been mapped, a central DNA flap has been identified, and class I integrase mutants have been validated. Vector systems with improved effectiveness and safety profiles are being applied by a number of laboratories in several pre-clinical models, with demonstrated efficacy in human tissues. The comparative lentivirological research that facilitates FIV vector development may also yield insights into the still enigmatic molecular basis for a signature lentiviral property with pathogenetic and therapeutic importance: permanent transgene integration in non-dividing cells. This review discusses virological aspects of lentiviral vector development, as well as some recent controversies and applications.

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Section: Optimization Of Fiv Vectorsmentioning

confidence: 56%

Section: Introductionmentioning

confidence: 99%

FIV: from lentivirus to lentivector

Saenz

Poeschla

2004

J. Gene Med.

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“…pCT5 (cytomegalovirus [CMV] promoter fused to the FIV R repeat at TATA box plasmid 5) is used to produce infectious, replication-competent FIV in human cells, which is enabled because the human cell-inactive 5= FIV U3 element was replaced with the human CMV (hCMV) promoter just upstream of the 5= R repeat (41,42). pCT5 was derived from the infectious 34TF10 molecular clone previously isolated from a lambda phage library by Talbott et al (53). Note that pCT5 encodes the wild-type (WT), normally infectious 34TF10 virus, since it expresses the full 34TF10 R-to-R proviral transcript with a normal 5= cap site and a normal 3= U3 (41,42).…”

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confidence: 99%

Feline Immunodeficiency Virus Gag Is a Nuclear Shuttling Protein

Kemler

Saenz

Poeschla

2012

J Virol

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Lentiviral genomic RNAs are encapsidated by the viral Gag protein during virion assembly. The intracellular location of the initial Gag-RNA interaction is unknown. We previously observed feline immunodeficiency virus (FIV) Gag accumulating at the nuclear envelope during live-cell imaging, which suggested that trafficking of human immunodeficiency virus type 1 (HIV-1) and FIV Gag may differ. Here we analyzed the nucleocytoplasmic transport properties of both Gag proteins. We discovered that inhibition of the CRM1 nuclear export pathway with leptomycin B causes FIV Gag but not HIV-1 Gag to accumulate in the nucleus. Virtually all FIV Gag rapidly became intranuclear when the CRM1 export pathway was blocked, implying that most if not all FIV Gag normally undergoes nuclear cycling. In FIV-infected feline cells, some intranuclear Gag was detected in the steady state without leptomycin B treatment. When expressed individually, the FIV matrix (MA), capsid (CA), and nucleocapsid-p2 (NC-p2) domains were not capable of mediating leptomycin B-sensitive nuclear export of a fluorescent protein. In contrast, CA-NC-p2 did mediate nuclear export, with MA being dispensable. We conclude that HIV-1 and FIV Gag differ strikingly in a key intracellular trafficking property. FIV Gag is a nuclear shuttling protein that utilizes the CRM1 nuclear export pathway, while HIV-1 Gag is excluded from the nucleus. These findings expand the spectrum of lentiviral Gag behaviors and raise the possibility that FIV genome encapsidation may initiate in the nucleus.G ag is both necessary and sufficient for retrovirus particle formation and budding. The protein is translated on free polysomes and targeted to the plasma membrane, where virus particles are assembled (16). A central question is whether Gag and the viral genomic RNA (gRNA) associate at the plasma membrane or earlier during assembly and, if so, whether this occurs in the cytosol; in association with organelles, e.g., cotranslationally; or even in the nucleus, as was described previously for an alpharetrovirus (17). Human immunodeficiency virus type 1 (HIV-1) gRNAs become anchored at the plasma membrane before particle assembly is detectable, but it is not clear whether the Gag-gRNA complexes of this and other lentiviruses first form in the cytoplasm and then transit to the plasma membrane or the gRNA traffics there independently (26,27). Biochemical experiments supported the former scenario, with a monomer or low-order multimers forming on HIV-1 gRNAs and higher-order multimer formation depending on subsequent plasma membrane interactions (33).Gag is encoded by the full-length unspliced viral RNA. To circumvent the cellular checkpoint that prevents the export of intron-containing mRNA, lentiviruses express Rev, which functions as an adaptor between the cellular karyopherin CRM1/exportin-1 and a Rev response element (RRE) located in the 3= region of unspliced viral RNAs (9). However, the main cellular function of the CRM1 nuclear export pathway is the export of cellular proteins containing a...

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“…Although FIV is not closely related to any previously identified virus, nucleotide sequence homology and genetic organization favour its classification within a subgroup of animal lentiviruses including equine infectious anaemia virus (EIAV) and visna virus (Talbott et al, 1989;Olmsted et al, 1989a, b;Phillips et al, 1990). In contrast to other members of this subgroup, FIV replicates readily in T lymphocytes and induces pathological changes closely similar to those seen in human AIDS.…”

Section: Introductionmentioning

confidence: 99%